Molecular contents are exchanged between organelles by the formation of membrane-enclosed vesicles that bud from one organelle and fuse with another. In principle, this process seems a simple one, yet it features many layers of regulation, with both protein and lipid components involved.

Our lab investigates the molecular mechanisms of membrane trafficking from endosomes to lysosomes, which have a major role in protein degradation. Transmembrane proteins ubiquitinated on their cytoplasmic domains are sorted into vesicles that bud into the lumen of endosomes, resulting in their degradation upon fusion of endosomes with lysosomes. Molecular recognition of ubiquitinated transmembrane proteins requires an elaborate machinery known as the endosomal sorting complexes required for transport (ESCRTs). The ESCRT machinery is highly conserved throughout eukaryotes, and defects in its function make profound contributions to human disease.

ESCRTs also have a role in the budding of transport vesicles that carry transmembrane proteins into the endosome lumen. Remarkably, this activity operates during cytokinesis to 'pinch' dividing cells apart, and enveloped viruses such as HIV exploit ESCRTs in order to pinch away the plasma membrane of infected cells.

Our research is currently focused on defining the activities of ESCRTs that execute membrane budding reactions. Our model system is the yeastSaccharomyces cerevisiae, which enables us to combine genetics with cell biology, biochemistry, and electron tomographic modeling of membrane structures.

Molecular mechanisms of membrane trafficking


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